Lab Notes: Skin Immune Cells Swing Both Ways

The skin's first line of defense, the Langerhans cells in the epidermis, is an MVP for versatility, researchers reported in Immunity.

The exact role of these cells has been controversial: do they suppress immune response to good bacteria or mobilize an attack against invaders? Part of the problem has been that most of the research had been done on skin cells from mice, whose Langerhans cells appear to function differently than in humans.

Using cells culled from human skin with a new technique, the researchers found that Langerhans cells actually hit either way as needed.

Under normal conditions, the specialized cells stimulated production of regulatory T cells to ward off an unnecessary immune response. But when a pathogen was present, Langerhans cells instead boosted effector memory T cells to ramp up the attack.

"This context-specific response is perfectly suited to a cell like the Langerhans cell which is at the interface of the body and the environment," lead author Thomas S. Kupper, MD, of Brigham and Women's Hospital in Boston, explained in a press release.

-- C.P.

Achilles Heel for Microbes

British researchers think they have found an Achilles heel shared by many pathogens – the need to hijack a host enzyme called calpain as part of their life cycle. In a series of experiments, investigators led by David Brough, PhD, of the University of Manchester found that blocking calpain in cells prevents Listeria monocytogenes from replicating.

The pathogen, responsible for the food-borne illness listeriosis, enters cells in vesicles called phagosomes, but must escape into the cytoplasm to replicate and cause disease. To do so, the bacterium recruits calpain to help blast its way out, although the exact mechanism remains unclear, the researchers reported in PLoS ONE.

In cells treated with a calpain inhibitor, L. monocytogenes was unable to escape, although other experiments showed that the inhibitor has no direct effect on the bacteria.

The finding may have broader implications than prevention of listeriosis; host calpain has been implicated in the life cycles of several other pathogens including malaria, toxoplasmosis, and coxsackievirus.

-- M.S.

Patching Beehives and Slowing Prostate Cancer

An over-the-counter health supplement made from honeybee hives may help stunt the growth of prostate cancer, researchers found.

Caffeic acid phenethyl ester (CAPE) – which is obtained from propolis, the substance bees use to patch holes in their hives – has been used as a natural remedy for a wide range of conditions, including sore throats, allergies, burns, and cancer.

Richard Jones, PhD, of the University of Chicago, and colleagues set out to study the anticancer claims. At low concentrations, CAPE halted the growth of human prostate cancer cells in culture. Tumors grafted into mice responded similarly to treatment, although CAPE did not kill the cancer cells. When treatment was stopped, the tumors resumed growing.

The researchers took a closer look at the cellular pathways affected by CAPE and found that the compound worked by impairing the ability of the cells to detect sources of nutrition, causing them to stop growing.

Writing in Cancer Prevention Research, the researchers said that CAPE may be a useful adjunct to therapies for prostate cancer and other malignancies.

-- T.N.

Hide-and-Seek with Cancer Stem Cells

Prostate cancer stem cells lurk in the last place where scientists might look: under the cover of low PSA production, according to a report in this month's issue of Cell Stem Cell.

Using a new technique to distinguish between low- and high PSA-producing cells, investigators found that cells with low-level antigen production were resistant to chemotherapy and thrived in response to hormonal therapy.

The findings point to a need to develop new therapeutic strategies that target low-PSA prostate cancer cells, according to Dean Tang, PhD, of the University of Texas MD Anderson Cancer Center in Houston.

The key to the discovery was development of a lentiviral reporter system that released green fluorescence protein in response to PSA expression in an infected cell. The system provided the first known means to characterize individual prostate cancer cells by PSA production.

Low-PSA cells divided slowly, expressed genes that conferred resistance to chemotherapy, and had minimal or no androgen receptors, making them insensitive to androgen ablation therapy. When the cells divided, they produced one identical copy and one PSA-positive cell.

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